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Drug X S-warfarin Agents that DECREASE metabolism (inhibit or compete for cytochrome P450) are more important than those that increase metabolism.

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Presentation on theme: "Drug X S-warfarin Agents that DECREASE metabolism (inhibit or compete for cytochrome P450) are more important than those that increase metabolism."— Presentation transcript:

1 Drug X S-warfarin Agents that DECREASE metabolism (inhibit or compete for cytochrome P450) are more important than those that increase metabolism

2 Drug X R-warfarin and S-warfarin Must also consider that both forms of warfarin can interact with other drugs

3 Both inhibitors and substrates of a particular CYP isozyme decrease the metabolism of substrates of that isozyme  increased efficacy Inducers increase the metabolism of substrates  decreased efficacy For example, for CYP 2C9, both amiodarone and carvedilol will increase the efficacy of celecoxib, but barbiturates will reduce it

4 In other words, drugs in the inhibitor and inducer columns can affect drugs in the substrate column, but substrates don’t affect inhibitors and inducers

5 Substrates can affect other substrates

6 Taking up the case of warfarin, the active enantiomer is S-warfarin which is metabolized by CYP 2C9.

7 That means we have to be most concerned by drugs that inhibit CYP 2C9 ---- i.e., amiodarone, cimetidine, etc., and especially fluvoxamine.

8 Drug X S-warfarin Drug X R&S-warfarin We also have to worry about drug interactions where warfarin causes an adverse drug interaction with another drug.

9 Neither warfarin enantiomer is an inducer or an inhibitor of CYP enzymes. So the drugs that could interact are ones that are substrates for the CYP isozymes that EITHER R- or S-warfarin is a substrate of. So you could expect interactions with amitriptyline, carvedilol, amitriptyline and alfentanil (reading just the first drug in the substrate list for each affected isozyme)


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